Exosomes released by macrophages contacting Trypanosoma cruzi attenuated or virulent strains deliver a different immunological message

ANDREA C. MESIAS; LEONARDO ACUÑA; CECILIA PEREZ BRANDAN; VALERIA TEKIEL; CECILIA PARODI

Buenos Aires

Otro; XXXIII Reunion anual de la Sociedad Argentina de Protozoologia; 2022

Sociedad Argentina de Protozoologia

Once a pathogen has overthrown the first defense barriers, a plethora of communication events operates at different layers to orchestrate an effective immune response. Extracellular vesicles (EVs) are indeed one key mechanism to re-transmit and amplify a message toward distal immune cells. Among the EVs diversity, exosomes are 50-150 nm vesicles originated from multivesicular bodies able to deliver cargos across long distances in a tightly regulated manner. Here we proposed to decode the message transmitted by exosomes produced by antigen-presenting cells in contact with infective Trypanosoma cruzi forms toward other naïve macrophages. With this purpose in mind, we have purified exosomes released by RAW 264.7 macrophages after their interplay with TCC or CL Brener (CLB) parasite strains. Our preliminary results showed that vesicles obtained from TCC- or CLB-infected cells trigger very different cytokine expression on the recipient cells. Macrophages stimulated with exosomes harvested from TCC-infected cells produced higher TNF-α release than those stimulated with EVs from CLB-infected cells, whereas an opposite response was observed for the secretion of regulatory cytokine IL-10. Further, the phagocytic function of the recipient cells was significantly diminished after stimulation with exosomes from TCC-infected macrophages. In an attempt to comprehend the different messages delivered, the protein cargo of exosomes was analyzed by a proteomic approach. The results showed a very distinct protein profile for these EVs subsets, considering both host and parasite origin assignments. So far, our findings suggest that macrophages which have faced T. cruzi entrance –either by infection or active phagocytosis– deliver a markedly different message to other naïve cell, depending on the parasite strain involved. Forthcoming experiments will help us understand how these messenger exosomes could impact on the host defense